There are a significant number of viruses that can infect dogs and/or cats. While symptoms due to the corresponding virus infections for example, can include mild cold-like symptoms, others can be rapidly fatal, as in the case of canine distemper virus (CDV) infections [see e.g., US2010/0196420]. Indeed, CDV triggers a multi-systemic infection that may involve the ocular, respiratory, gastrointestinal, integument, and nervous systems. The mortality rate from canine parvovirus (CPV) is also relatively high [see e.g., US2009/0010955]. CPV is primarily an enteric pathogen that infects dogs, especially young dogs, and is characterized by acute diarrhea, fever, and leukopenia in dogs and puppies more than 4 to 5 weeks old. Even younger puppies can suffer myocardial disease. Canine distemper virus and canine parvovirus are the two most important canine viruses to protect puppies/dogs from.
Additional canine viruses include: canine parainfluenza (CPI) virus, which is a highly contagious virus that causes respiratory illnesses contributing to the contraction of upper respiratory diseases and infectious tracheobronchitis; canine adenovirus type-1 (CAV1) which leads to infectious hepatitis; and canine influenza virus (CIV) which is highly contagious and can cause a severe type of respiratory disease. CIV has been reported to be capable of causing 100% infection with 80% morbidity, and up to 5-8% mortality in severe infections [Crawford et al., Science 310(5747):482-485 (2005); U.S. Pat. No. 7,959,929 B2]. Similarly, there are a number of feline viruses that afflict cats including feline calicivirus (FCV), feline leukemia virus (FeLV), feline panleukopenia virus (FPLV), feline coronavirus (FCoV), and feline rhinotracheitis (FVR) virus.
It is now widely accepted that the best way of preventing disease due to canine or feline virus infections is to vaccinate them against these viruses. Indeed, canine distemper virus vaccines have significantly reduced the prevalence of the corresponding disease. Similarly, infectious canine hepatitis has been extremely limited by canine adenovirus-2 vaccines (CAV2). The use of live attenuated CAV2 in vaccines in place of closely related CAV1 eliminates concerns regarding the interstitial nephritis and corneal opacity observed in dogs that have been inoculated with live attenuated CAV1 [Taguchi et al., Can Vet J. 52(9): 983-986 (2011)].
Moreover, multivalent live attenuated virus vaccines can be safely administered that limit the number of vaccine injections required. Accordingly, there are several commercially available multivalent live attenuated virus vaccines that protect against canine distemper, canine infectious hepatitis, canine parvovirus, and canine parainfluenza virus. In addition, newer multivalent vaccines further protect against canine influenza virus as well.
Heretofore, attenuated canine and feline viruses have been unstable when stored in liquid solutions. Therefore, most live attenuated canine or feline virus vaccines are lyophilized, i.e., freeze-dried, prior to their long-term storage. The live attenuated canine or feline virus is commonly mixed as a suspension in water with a protective agent, frozen, and then dehydrated by sublimation and secondary drying during the lyophilization process. The low temperatures of freezing and drying by sublimation, together with the low surface to volume ratios involved, can require long drying periods and thereby, significantly increase manufacturing time and costs.
In addition, there are inherent inconsistencies in large commercial drying processes due to: the inability to adjust the shelf temperature across the entire product load, variable freezing rates across the dryer, edge effects, and radiant energy effects. Increasing the drying temperature to reduce drying times is often not an option since the drying temperature has to remain significantly below the glass-transition temperature of the protective protein matrix. Moreover, the long inconsistent drying times and/or high drying temperatures often lead to structural damage to the live attenuated viruses, along with a significant loss of their biologic activity.
Consequently, in order to account for the inherent loss in efficacy, lyophilized canine and/or feline vaccines that comprise live attenuated viruses are stored with augmented titers. However, such increased titers can lead to significant adverse events should the lyophilization process actually lead to less loss of activity than anticipated. Therefore, great care is required to formulate a vaccine to contain a virus titer that is not only safely below the amount that leads to adverse events, but that also maintains sufficient efficacy in view of the virus titer loss due to lyophilisation and subsequent storage. Therefore, there is a need for new live attenuated canine and/or feline virus vaccines that can reliably retain their virus titers at a safe and efficacious level.
The citation of any reference herein should not be construed as an admission that such reference is available as “prior art” to the instant application.